We've had people stay in the Upper Keys, (Key Largo/Tavernier/Islamorada) and do day trips down to Key West. Remember it's some 90 miles to Key West and it's mostly a two lane highway with max speed limits of 55mph.
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AND it is a LONG boring drive. I will NEVER drive to Key West again ... they do have an airport, and flights from Miami international only take less than 30 minutes ..
I dove with Pirates Cove in Key West earlier this year ... they were real professional, and do two tank dives in both the morning and the afternoon. I LOVE Key West ... the night life there is good, lots to do, excellent resturants and hotels. We stayed at the Hilton on the beach, which was an OK hotel ... next time down there, probably will stay with Marriott ...